The long range objective of this research is to elucidate the pathophysiological mechanisms of vulvodynia, a chronic pain syndrome of the vaginal and vulvar area, in order to develop improved treatment strategies for alleviating chronic pain in these women, targeted at the underlying pathophysiological mechanisms. Vulvodynia is a major challenge for women who suffer from this chronic pain syndrome, and has a detrimental impact on their sexual lives. Treatment strategies, including medical and surgical approaches, are empirical only and are often unsuccessful. We propose two approaches to gain a better understanding of the pathophysiological mechanisms of vulvodynia: (1) We will develop an animal model in the rat, that will allow to study the spinal cord pathways involved in the processing of noxious input from the vagina. The specific goals of this animal research project are (a) to obtain detailed information about the spinal cord pathways that process nociceptive afferent input from the vaginal area, (b) to determine the influence of the estrous cycle on the spinal cord processing of noxious vaginal stimulation, (c) to assess the effects of pharmacological agents on the spinal cord processing of noxious vaginal stimulation, (d) to study the influence of previous vaginal/vulvar trauma on the response to noxious vaginal stimulation. (2) We propose to characterize pain in patients with vulvodynia in detail. Our hypothesis is that patients with vulvodynia can be differentiated into distinct groups based on their pain characteristics, and that treatment of pain in vulvodynia will be more effective, if based on recognition of the underlying neurophysiological mechanisms. The specific goals of this clinical research project are to (a) to assess the response to non-noxious and noxious stimuli in the vulvar and vaginal area in women suffering from vulvodynia in comparison to healthy controls using quantitative sensory testing, (b) to determine the influence of the gonadal hormonal milieu on pain in patients with vulvodynia. These studies will provide fundamental new insights into the pathophysiological mechanisms of vulvodynia. The results of these studies may rapidly contribute to the design of new treatment strategies specifically targeted at the underlying neural mechanisms of chronic pain in women with vulvodynia.